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What is hyperplasia primarily characterized by?
What type of hyperplasia occurs when tissue is removed or damaged?
What is metaplasia?
Which of the following is NOT a component of the inflammatory response?
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What is the first step in the inflammatory response?
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What is the role of proteoglycans in the extracellular matrix (ECM)?
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Which type of inflammation is characterized by the presence of purulent exudates?
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What is primarily observed in fibrinous inflammation?
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What is a common outcome when the ECM is damaged?
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What distinguishes primary union (first intention) from secondary union (second intention)?
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What condition is known for excessive production of ECM leading to keloids?
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What effect does diabetes have on cutaneous wound healing?
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How is neoplasia defined?
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What characterizes cancer cells in terms of cell division?
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How does the incidence of cancer relate to age?
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What is the role of tumor suppressor genes in cancer development?
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What type of genetic alteration is often linked to the overexpression of oncogenes?
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What is a common characteristic of familial cancers?
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Which of the following statements about miRNAs and carcinogenesis is accurate?
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What typically causes the epigenetic silencing of tumor suppressor genes?
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What is a common factor that contributes to the risk of cancer development in certain diseases?
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In familial cases of tumor development, what happens to the tumor suppressor genes?
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What characterizes benign tumors?
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Which of the following is NOT a characteristic of malignant tumors?
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What term is used for a mass that projects above the mucosal surface?
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Which of these conditions is considered an acquired preneoplastic disorder?
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Which suffix is typically used to name benign tumors?
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What does dysplasia refer to in the context of tumors?
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What is the term for secondary implants that are discontinuous with the primary tumor?
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What is the most common mechanism by which sarcomas spread?
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Which step in the invasion of the extracellular matrix involves tumor cells detaching from each other?
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What triggers the process of angiogenesis in tumors?
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What role do metalloproteinases play in tumor cell invasion?
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Which of the following best describes vascular dissemination?
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Which organ is the most common site for metastatic spread from primary tumors?
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What is the role of p53 in tumor angiogenesis?
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During which step of tissue invasion do tumor cells migrate toward new locations?
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What is the first effect of hypoxia on cellular metabolism?
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Which of the following is a characteristic of irreversible injury in cells?
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What role do oxygen free radicals play in cellular injury?
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What occurs as a result of ATP depletion in cells during ischemia?
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What is a consequence of prolonged hypoxia on the cytoskeleton?
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Which of the following contributes to the formation of cell surface blebs during hypoxia?
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What happens to lysosomes during irreversible injury?
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What is an effect of the influx of calcium during ischemic injury?
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What is the primary distinction between hyperplasia and hypertrophy?
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What triggers compensatory hyperplasia in tissues?
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Which process involves the replacement of one adult cell type with another in response to stress?
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What are the primary components involved in the inflammatory response?
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Which of the following steps is NOT part of the inflammatory response?
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What is fatty change most often associated with?
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Which of the following conditions can lead to fatty change in cells?
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What is the primary effect of severe fatty change on cellular function?
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How do macrophages contribute to lipid accumulation in tissues?
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What do xanthomas represent in the body?
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What type of pigment accumulation is primarily found in basal cells of the epidermis?
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In which condition is glycogen accumulation mostly observed?
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What is pathologic calcification primarily characterized by?
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What term describes the deposition of calcium in dead or dying tissues, despite normal serum calcium levels?
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Which of the following is NOT a cause of hypercalcæmia?
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In which tissues is metastatic calcification most commonly observed?
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What is atrophy characterized by?
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Which of the following correctly describes hypertrophy?
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What physiological condition can lead to atrophy as a cellular response?
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Which cellular adaptation occurs mainly in response to an increased workload?
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What is a characteristic of metastatic calcification?
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What is the primary role of CD4+ T cells in the immune response?
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How do CD8+ T cells primarily function in the immune system?
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Which cytokines are mainly produced by T-helper-2 (TH2) cells?
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What is required for complete activation of T cells during the immune response?
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What percentage of circulating lymphocytes do B-lymphocytes constitute?
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Which immunoglobulin class is primarily secreted by plasma cells?
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What role do macrophages play in the immune response?
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Which receptor on B cells helps bind to Epstein-Barr virus (EBV)?
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Study Notes
Cellular Adaptations
- Hypertrophy: Increase in cell size, caused by increased functional demand or hormonal stimulation. Example: Uterine smooth muscle hypertrophy during pregnancy.
- Hyperplasia: Increase in the number of cells, often occurs alongside hypertrophy. Example: Compensatory hyperplasia in the liver after partial resection.
- Metaplasia: Reversible change in which one adult cell type is replaced by another, often in response to chronic stress. Example: Replacement of ciliated columnar epithelium in the bronchus with stratified squamous epithelium due to smoking.
Inflammation
- Complex host response to injury or infection, involving vascular and cellular reactions.
- Purpose: Remove injurious agents, necrotic cells and tissues.
- Main Components: Vascular reaction and cellular response, mediated by plasma proteins and cells.
- Steps: Recognition, leukocyte recruitment, agent removal, response regulation, and resolution/repair.
- Role in Tissue Repair: Provides a substrate for cell growth and formation of tissue microenvironments, regulating cell proliferation and differentiation.
Morphologic Patterns of Inflammation
- Serous: Watery, protein-poor fluid effusion, seen in peritoneal, pleural, or pericardial cavities.
- Fibrinous: Formation of fibrin meshwork or coagulum, indicative of severe injury. Can be removed by macrophages or fibrinolysis, or replaced by fibrosis.
- Suppurative (Purulent): Presence of purulent exudate (pus), consisting of neutrophils, necrotic cells, and fluid, often caused by bacteria. Abscess: localized collection of pus.
- Ulceration: Erosion of an epithelial surface due to necrosis, with associated subepithelial inflammation.
Wound Healing
- Primary Union (First Intention): Occurs in clean, incised wounds with minimal tissue loss.
- Secondary Union (Second Intention): Occurs in wounds with extensive tissue loss, resulting in more scarring and wound contraction.
- Factors Affecting Healing: Infection, diabetes, type/volume/location of injury.
- Keloid: Excessive ECM production in the skin, leading to raised scars.
Neoplasia
- Definition: New and abnormal tissue growth, uncoordinated with normal tissue.
- General Characteristics: Unresponsive to normal growth control, competes with normal cells for resources, autonomous growth, and may require endocrine stimulation.
Epidemiology of Cancer
- Incidence: Varies with age, race, geographic factors, and genetic background.
- Most Common: At the extremes of age.
- Geographic Variation: Mostly due to environmental exposures.
- Sporadic vs. Familial: Most cancers are sporadic, while some are familial.
- Hereditary Cancer: Autosomal dominant (linked to germline mutations in tumor suppressor genes) or autosomal recessive (associated with DNA repair defects).
- Preneoplastic Disorders: Increased risk of developing cancer (e.g., chronic gastritis, ulcerative colitis).
Genetic Lesions in Cancer
- Mutations: Point mutations, chromosomal abnormalities (translocations, deletions, amplifications).
- Translocations: Overexpression of oncogenes or generation of novel fusion proteins.
- Deletions: Affect tumor suppressor genes.
- Amplifications: Increase expression of oncogenes.
- miRNA: Overexpression can reduce expression of tumor suppressors, while deletion/loss of expression can lead to overexpression of proto-oncogenes.
- Epigenetic Changes: Reversible, heritable changes in gene expression, often involving methylation of promoter regions, silencing tumor suppressor or DNA repair genes.
Insensitivity to Growth Inhibitory Signals
- Tumor Suppressor Genes: Encode proteins that inhibit cell proliferation by regulating the cell cycle.
- Gene Loss: Both copies of the gene must be inactivated for tumor development to occur.
- Familial Predisposition: Inherit one defective copy, lose the second through somatic mutation.
- Sporadic Cases: Both copies are lost through somatic mutations.
Tumor Classification
- Benign Tumors: Localized, non-spreading, may cause local effects.
- Malignant Tumors (Cancers): Invade and destroy surrounding tissue, spread to distant sites (metastasize).
Benign Tumor Characteristics
- Resemble normal cells morphologically and functionally.
- Well-differentiated cells.
- Scanty, normal mitoses.
- Slow growth, localized, non-infiltrative.
Acquired Preneoplastic Disorders
- Persistent regenerative cell replication (skin ulcer, cirrhosis).
- Hyperplastic and dysplastic proliferations (endometrial hyperplasia, dysplastic changes in the bronchus).
- Chronic atrophic gastritis.
- Chronic ulcerative colitis.
- Leukoplakia of the oral cavity.
- Villous adenomas of the colon.
Nomenclature of Benign Tumors
- Cell type + "-oma" suffix (fibroma, chondroma, leiomyoma).
- Based on cell origin:
- Adenoma: glandular pattern
- Papilloma: epithelial surfaces with finger-like structures
- Polyp: Mass projecting above mucosal surface
- Cystadenomas: Hollow cystic masses (e.g., in ovary)
- Fibroadenoma of the breast: Mixed type
Malignant Tumor Characteristics
- Pleomorphism: Variation in size and shape.
- Hyperchromasia: Increased nuclear pigmentation.
- High Nuclear/Cytoplasmic (N/C) Ratio.
- Giant Cells: Contain multiple nuclei.
- Nuclear Pleomorphism: Coarse and clumped chromatin.
- Atypical Mitoses: Numerous and abnormal mitoses.
- Loss of Polarity: Cells lack normal orientation pattern.
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Dysplasia: Loss of cell uniformity and architectural orientation.
- Carcinoma in situ: dysplasia affecting the entire thickness of the epithelium.
- Rapid Growth: Infiltration, invasion, destruction, and penetration of surrounding tissues.
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Metastasis: Secondary implants discontinuous with the primary tumor.
- Pathways: Seeding within body cavities, lymphatic spread (carcinomas), hematogenous spread (sarcomas and some carcinomas).
- Frequent metastatic sites: Liver and lungs.
Mechanisms of Local and Distant Spread
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Invasion of ECM: Tumour cells reach the basement membrane, invade interstitial connective tissue, and penetrate blood vessel basement membranes.
- Stages:
- Detachment of tumour cells by loss of surface E-cadherins.
- Attachment of tumour cells to matrix components.
- Degradation of ECM by tumour and fibroblast-produced proteases.
- Migration of tumour cells.
- Stages:
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Vascular Dissemination:
- Intravasation: Degradation of blood vessels' basement membrane, forming tumour emboli.
- Extravasation: Adhesion to endothelium followed by transgression through basement membrane.
Development of Sustained Angiogenesis
- Essential for Tumor Growth: Controlled by balance between angiogenic and antiangiogenic factors.
- Hypoxia: Triggers angiogenesis through HIF-1α and VEGF.
- Factors Regulating Angiogenesis: p53, other pro-angiogenic and antiangiogenic factors.
Invasion and Metastasis
- Invasion: Tumour cells loosen cell-cell contacts, degrade ECM, attach to new ECM components, and migrate.
- ECM Degradation: Mediated by proteolytic enzymes (MMPs) secreted by tumour and stromal cells, releasing sequestered growth factors and creating chemotactic and angiogenic fragments.
- Metastatic Site: Often predictable based on primary tumour location.
- First Capillary Bed Encounter: Lung and liver are most common metastatic sites.
Ischemia and Hypoxic Injury
- Ischemia or toxins allow an influx of calcium from the extracellular space into the cell, causing the release of mitochondrial calcium.
- This activates various enzymes like phospholipases, proteases, ATPases and endonucleases.
- Phospholipases degrade cell membranes.
- Proteases catabolize structural proteins.
- ATPases lead to ATP depletion.
- Endonucleases fragment DNA.
- The generation of oxygen free radicals is an important mediator of cell death.
Reversible Injury
- Hypoxia affects aerobic respiration, reducing intracellular ATP.
- Reduced ATP leads to an influx of extracellular calcium.
- Reduced ATP also reduces the plasma membrane sodium pump, causing intracellular sodium accumulation and potassium diffusion out of the cell.
- This results in isosmotic water gain and acute cellular swelling.
- Metabolites like inorganic phosphates, lactic acid and purine nucleotides accumulate.
- Decreased ATP and AMP stimulate phosphofructokinase, increasing anaerobic glycolysis.
- This depletes glycogen and causes accumulation of lactic acid and inorganic phosphates, reducing intracellular pH.
- Detachment of ribosomes from RER occurs, reducing protein synthesis.
- If hypoxia persists, the cytoskeleton disappears, leading to loss of ultrastructural features like microvilli and the formation of cell surface blebs.
Irreversible Injury
- Irreversible injury is associated with severe mitochondrial vacuolization, calcium particle accumulation, extensive plasma membrane damage, lysosomal swelling, and reperfusion injury.
- Loss of proteins, coenzymes and RNA occurs from the hyperpermeable membrane.
- Lysosomal enzymes leak into the cytoplasm, are activated by the reduced pH and degrade cytoplasmic components.
- Dead cells may be replaced by whorled masses of phospholipids (myelin figures).
Mechanisms of Irreversible Injury
- Progressive loss of membrane phospholipids.
- Cytoskeletal abnormalities caused by activation of proteases and increased calcium levels.
- Toxic oxygen radicals generated after reperfusion of the ischemic area, released by influxed neutrophils.
- Lipid breakdown products have detergent effects.
Abnormal Exogenous Substance Deposit
- Occurs when the cell lacks the enzymatic machinery or the ability to transport the substance to other sites.
- Fatty change (steatosis) refers to the abnormal accumulation of triglycerides within parenchymal cells.
Fatty Change
- Most commonly seen in the liver.
- Reversible but can occur in the heart, skeletal muscle, kidney and other organs.
- Caused by toxins, diabetes mellitus, protein malnutrition, obesity and anoxia.
- Excess accumulation of triglycerides can result from defects at any step from fatty acid entry to synthesis of lipoproteins.
- Hepatotoxins like alcohol alter mitochondrial and SER function.
- CCl4 and protein malnutrition decrease synthesis of apoproteins.
- Anoxia inhibits fatty acid oxidation.
- Starvation increases fatty acid mobilization from peripheral stores.
- Mild fatty change has no effect on cellular function.
- More severe changes can transiently impair cellular function.
- Grossly, the liver enlarges and becomes progressively yellow.
- Microscopically, small vacuoles appear in the cytoplasm around the nucleus, which coalesce to create clear spaces, displacing the nucleus to the periphery.
Cholesterol and Cholesterol Esters
- Macrophages in contact with lipid debris of necrotic cells become stuffed with lipid, appearing as foamy cells.
- In atherosclerosis, smooth muscle cells and macrophages fill with lipid vacuoles composed of cholesterol and cholesterol esters.
- Xanthomas are accumulations of fat within macrophages of subcutaneous connective tissues, appearing as white nodules.
Proteins
- Less commonly seen, e.g. in glomerular diseases with proteinuria, accumulating in proximal convoluted tubules.
Glycogen
- Seen in cases of abnormal metabolism of glucose or glycogen.
- Appear under the light microscope as vacuoles.
Pigments
- Colored substances either exogenous or endogenous.
- Melanin accumulates in basal cells of the epidermis resulting in freckles or in dermal macrophages.
- Hemosiderin is a hemoglobin-derived granular pigment, golden brown, that accumulates in tissues when there is local or systemic excess iron.
Pathologic Calcification
- Abnormal accumulation of calcium salts, with smaller amounts of iron, magnesium and other minerals.
- Dystrophic calcification occurs in dead or dying tissues, despite normal serum levels of calcium and in the absence of calcium metabolic derangement.
- Encountered in areas of necrosis, seen in atheromas of advanced atherosclerosis on areas of intimal injuries of large arteries.
- Also seen in aging and in aortic valves.
- Appears as intracellular or extracellular basophilic deposits, sometimes heterotopic bone may be formed.
- Metastatic calcification may occur in normal tissues whenever there is hypercalcemia.
Causes of Hypercalcemia
- Primary endocrine dysfunction (e.g. hyperparathyroidism).
- Tumors associated with increased bone catabolism (e.g. multiple myeloma, metastatic cancer and leukemia).
- Ingested exogenous substances resulting in vitamin D intoxication or milk alkali syndrome.
- Sarcoidosis.
- Advanced renal failure where the resulting phosphate retention leads to secondary hyperparathyroidism.
Metastatic Calcification
- May occur widely in tissues, principally in the interstitial tissues, kidneys, lungs and gastric mucosa.
- Usually does not cause significant impairment of organ function.
- In extensive nephrocalcinosis, some impairment may occur.
Cellular Adaptations of Growth and Differentiation
- Physiologic adaptations are responses of cells to normal stimulations by hormones or endogenous chemicals (e.g. induction of breast growth and lactation).
- Pathologic adaptations often share the same underlying mechanisms, but they allow the cells to modulate their environment and hopefully escape injury.
Atrophy
- Shrinkage in the size of the cell by loss of cell substance, may involve the entire organ.
- Atrophied cells have diminished function but are not dead.
- Apoptotic death may also be induced by the same signals that cause atrophy.
Causes of Atrophy
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Decreased workload.
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Loss of innervation.
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Diminished blood supply.
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Inadequate nutrition.
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Loss of endocrine stimulation.
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Aging.
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Cells become smaller in size to achieve equilibrium between cell size and diminished blood supply, nutrition or trophic stimulation.
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Biochemically, there is decreased synthesis, increased catabolism, or both.
Hypertrophy
- Increase in the size of cells by increased synthesis of structural proteins and organelles, leading to an increase in the size of the organ.
- Can be physiologic or pathologic, caused by increased functional demand or specific hormonal stimulation (e.g. hypertrophy of smooth muscles of the uterus during pregnancy).
Hyperplasia
- Increase in the number of cells in an organ or tissue.
- Hypertrophy and hyperplasia are closely related and often develop concurrently in tissues.
- Hyperplasia can be physiologic or pathologic.
Types of Physiologic Hyperplasia
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Hormonal hyperplasia
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Compensatory hyperplasia, occurs when a portion of tissue is removed or diseased.
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Most cases of pathologic hyperplasia are due to excessive hormonal or growth factor stimulation.
Metaplasia
- Reversible change in which one adult cell type is replaced by another adult cell type, another cellular adaptation where cells sensitive to a particular stress are replaced by other cell types able to withstand the adverse environment.
Inflammation
- Host response to foreign invaders and necrotic tissue, but it is itself capable of causing tissue damage.
- It is a reaction of tissues to various injurious stimuli.
- It is a protective response to remove the initial cause of cell injury, necrotic cells and tissues.
- It can have harmful effects like anaphylactic shock, rheumatoid arthritis and atherosclerosis.
Main Components of Inflammation
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Vascular reaction.
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Cellular response.
-
Both are activated by mediators derived from plasma proteins and various cells.
Steps of the Inflammatory Response
- Recognition of the injurious agent.
- Recruitment of leukocytes.
- Removal of the agent.
- Regulation (control) of the response.
- Resolution (repair).
CD4 and CD8 Molecules
- CD4 is present in about 60% of T cells, while CD8 is present in about 30%.
- CD4:CD8 ratio is about 2:1.
- CD4 molecule binds to class II MHC molecule expressed on antigen presenting cells.
- CD8 binds to class I MHC molecules.
T Helper Cells (TH cells)
- Two subsets: T-helper-1 (TH1) and T-helper-2 (TH2).
- TH1 cells produce IL-2 and interferon-γ (IFN-γ), but not IL-4 or IL-5.
- TH2 cells produce IL-4, IL-5 and IL-13, but not IL-2 or IFN-γ.
- TH1 cells facilitate delayed hypersensitivity, macrophage activation, and synthesis of opsonizing and complement-fixing antibodies.
- TH2 cells aid in the synthesis of other classes of antibodies, and in the activation of eosinophils.
CD8+ T Cells
- Mainly function as cytotoxic cells to kill other cells.
- Like CD4+ T cells, they can secrete cytokines, primarily of the TH1 type.
T Cell Activation
- T cells require two signals for complete activation during antigen recognition.
- Engagement of TCR by appropriate MHC-antigen complex with CD4 and CD8 coreceptors.
- Interaction of CD28 on T cells with CD80 or CD86 on antigen-presenting cells.
- In the absence of this second signal, T cells undergo apoptosis or become unreactive (anergic), preventing autoimmunity.
B Lymphocytes
- Constitute 10-20% of circulating lymphocytes.
- Found in the superficial cortex of lymph nodes and the white pulp of the spleen.
- Form lymphoid aggregates which when activated form germinal centers.
- After antigen stimulation, B-cells transform into plasma cells that secrete immunoglobulins (IgG, IgM, IgA), constituting 95% of plasma immunoglobulins.
- IgE occurs in traces in the serum, while IgD is only cell-bound to B cells.
- Monomeric IgM is present on the surface of all B cells, forming an antigen receptor of B cells (BCR).
- Somatic rearrangement of immunoglobulin genes results in unique antigen specificity.
- Several other molecules are expressed on B cells including CD 19 and CD20.
- CD21 serves as a complement receptor and also binds to Epstein-Barr virus (EBV).
- CD40 interacts with CD154 on activated T-lymphocytes.
Macrophages
- Play several roles in immune response:
- Present antigens to T-cells through class II MHC molecules.
- Production of cytokines that influence the function of T and B cells, endothelial cells and fibroblasts.
- Secretion of toxic metabolites and proteolytic enzymes which lyse tumor cells.
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Description
Test your knowledge on cellular adaptations such as hypertrophy, hyperplasia, and metaplasia, along with the complex biological response of inflammation. This quiz covers key concepts and examples that illustrate these important physiological processes. Enhance your understanding of how the body responds to injury and stress at the cellular level.
